ArticleArteriosclerosis, thrombosis, and vascular biology2020
Myristoylation of LMCD1 Leads to Its Species-Specific Derepression of E2F1 and NFATc1 in the Modulation of CDC6 and IL-33 Expression During Development of Vascular Lesions.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 15 citations in OpenAlex.
- Role of LMCD1 in the Long-Term Effects of Angiotensin II in Vascular Smooth Muscle Cells.International journal of molecular sciences · 2025Article
- Review
- Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Integrative analysis of HASMCs gene expression profile revealed the role of thrombin in the pathogenesis of atherosclerosis.BMC cardiovascular disorders · 2023Article
- Blockade of CD47 function attenuates restenosis by promoting smooth muscle cell efferocytosis and inhibiting their migration and proliferation.The Journal of biological chemistry · 2023Article
- Novel Role of Prereplication Complex Component Cell Division Cycle 6 in Retinal Neovascularization.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
- The Paradigm Change of IL-33 in Vascular Biology.International journal of molecular sciences · 2021Review
- A Not-So-Ancient Grease History: Click Chemistry and Protein Lipid Modifications.Chemical reviews · 2021Review
- An autophagy-related prognostic signature associated with immune microenvironment features of uveal melanoma.Bioscience reports · 2021Article
- A Novel Plant Leaf Patch Absorbed With IL-33 Antibody Decreases Venous Neointimal hyperplasia.Frontiers in bioengineering and biotechnology · 2021Article
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
objectiveIn view of our previous observations on differential expression of LMCD1 (LIM and cysteine-rich domains 1) in human versus rodents, we asked the question whether LMCD1 plays a species-specific role in the development of vascular lesions. Approach and Results: A combination of genetic, molecular, cellular, and disease models were used to test species-specific role of LMCD1 in the pathogenesis of vascular lesions. Here, we report species-specific regulation of LMCD1 expression in mediating vascular smooth muscle cell proliferation and migration during vascular wall remodeling in humans versus mice. Thrombin induced LMCD1 expression in human aortic smooth muscle cells but not mouse aortic smooth muscle cells via activation of Par1 (protease-activated receptor 1)-Gαq/11 (Gα protein q/11)-PLCβ3 (phospholipase Cβ3)-NFATc1 (nuclear factor of activated T cells 1) signaling. Furthermore, although LMCD1 mediates thrombin-induced proliferation and migration of both human aortic smooth muscle cells and mouse aortic smooth muscle cells via influencing E2F1 (E2F transcription factor 1)-mediated CDC6 (cell division cycle 6) expression and NFATc1-mediated IL (interleukin)-33 expression, respectively, in humans, it acts as an activator, and in mice, it acts as a repressor of these transcriptional factors. Interestingly, LMCD1 repressor activity was nullified by N-myristoyltransferase 2-mediated myristoylation in mouse. Besides, we found increased expression of LMCD1 in human stenotic arteries as compared to nonstenotic arteries. On the other hand, LMCD1 expression was decreased in neointimal lesions of mouse injured arteries as compared to noninjured arteries.
conclusionsTogether, these observations reveal that LMCD1 acts as an activator and repressor of E2F1 and NFATc1 in humans and mice, respectively, in the induction of CDC6 and IL-33 expression during development of vascular lesions. Based on these findings, LMCD could be a potential target for drug development against restenosis and atherosclerosis in humans.
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